HIV-1 DNA/MVA vaccination reduces the per exposure probability of infection during repeated mucosal SHIV challenges
HIV-1 DNA/MVA vaccination reduces the per exposure probability of infection during repeated mucosal SHIV challenges
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DOI：
10.1016/j.virol.2006.04.005
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发表时间：
2006-08-15
期刊：
影响因子：
3.7
通讯作者：
Butera, Salvatore
中科院分区：
文献类型：
--
作者：
Ellenberger, Dennis;Otten, Ronald A.;Butera, Salvatore
从历史上看，专门设计用于提高细胞免疫力的HIV疫苗在单次高病毒暴露的猴子中进行测试时，可以防止疾病进展，但不能防止感染。另一种更类似于人类性接触的方法是用低得多的病毒剂量重复攻击免疫猴，直到记录到全身感染。使用这些条件来模拟人类性传播，我们发现，多蛋白DNA/MVA HIV-1疫苗确实能够保护恒河猴免受系统性感染时，反复挑战与高度异源性免疫缺陷病毒（SHIV）。此外，这种重复的挑战方法使我们能够计算每次暴露的感染概率，观察到的疫苗效力为64%，并根据实现感染所需的暴露对保护的相关性进行系统分析。因此，改进的非人灵长类动物疫苗有效性模型可以提供新的见解，并可能重新对人类HIV临床试验的积极结果的期望。(c)2006年爱思唯尔公司All rights reserved.
Historically, HIV vaccines specifically designed to raise cellular immunity resulted in protection from disease progression but not infection when tested in monkeys challenged with a single high virus exposure. An alternative approach, more analogous to human sexual exposures, is to repetitively challenge immunized monkeys with a much lower dose of virus until systemic infection is documented. Using these conditions to mimic human sexual transmission, we found that a multi-protein DNA/MVA HIV-1 vaccine is indeed capable of protecting rhesus monkeys against systemic infection when repeatedly challenged with a highly heterologous immunodeficiency virus (SHIV). Furthermore, this repetitive challenge approach allowed us to calculate per-exposure probability of infection, an observed vaccine efficacy of 64%, and undertake a systematic analysis for correlates of protection based on exposures needed to achieve infection. Therefore, improved non-human primate models for vaccine efficacy can provide novel insight and perhaps renew expectations for positive outcomes of human HIV clinical trials. (c) 2006 Elsevier Inc. All rights reserved.